The purpose of this proposal is to investigate the pathophysiology of exercise-induced asthma. The first set of studies will be concerned with measuring the interaction of an exercise stimulus with environmental factors such as cold, heat and humidity, and the mechanisms by which they operate. The second series of investigations will be concerned with determining if exercise produces acute bronchoconstriction in a dose-response fashion or wheter it is a threshold effect. When this is known we propose to determine if the stimulus-response relationship can be modified with training and/or therapy. When this information is known, we will then evaluate whether a refractory period develops to repetitive exercise challenges and its clinical and physiologic significance. The final studies will be concerned with the mechanisms of exercise-induced asthma. They will consist of experiments designed (1) to look for the release of mmdiators of immediate hypersensitivity in arterial blood in response to an exercise challenge, (2) to evaluate whether exercise activates the complement system, and (3) to determine if blood draining an exercising muscle contains any substance capable of contracting smooth muscle.